HOMOPURINE AND HOMOPYRIMIDINE STRANDS COMPLEMENTARY IN PARALLEL ORIENTATION FORM AN ANTIPARALLEL DUPLEX AT NEUTRAL PH WITH A-C, G-T, AND T-C MISMATCHED BASE-PAIRS

DNA sequences d-TCAGGAAAGAAGGT (a 14-mer) and d-CTCCTTITCTTCC (a 12-me r) are complementary in parallel orientation forming either Donohue (r everse Watson-Crick) base pairing at neutral pH or Hoogsteen base pair ing at slightly acidic pH. The structure of the complex formed by diss olving the two strands in equimolar ratio in water has been investigat ed by nmr. At neutral pH, the system forms an ordered antiparallel dup lex with five A : T and four G : C Watson-Crick base pairs and three m ismatches, namely G-T, AC, and T-C. The nuclear Overhauser effect cros s-peak pattern suggests an overall B-DNA conformation with major struc tural perturbations near the mismatches. The duplex has a low melting point and dissociates directly into single strands with a broad meltin g profile. The hydrogen-bonding schemes in the mismatched base pairs h ave been investigated. It has been shown earlier that in acidic pH, th e system prefers a triple-stranded structure with two pyrimidine stran ds and one purine strand. One of the pyrimidine strands has protonated cytosines, forms Hoogsteen base pairing, and is aligned parallel to t he purine strand; the other has nonprotonated cytosines and has base-p airing scheme similar to the one discussed in this paper. The parallel duplex is therefore less stable than either the antiparallel duplex o r the triplex, in spite of its perfect complementarity. (C) 1997 John Wiley & Sons, Inc.